Possible novel mechanism for bitter taste mediated through cGMP

Taste is the least understood among sensory systems, and bitter taste mecha nisms pose a special challenge because they are elicited by a large variety of compounds. We studied bitter taste signal transduction with the quench- flow method and monitored the rapid kinetics of the second messenger guanos ine 3',5'-cyclic monophosphate (cGMP) production and degradation in mouse t aste tissue. In response to the bitter stimulants, caffeine and theophyllin e but not strychnine or denatonium cGMP levels demonstrated a rapid and tra nsient increase that peaked at 50 ms and gradually declined throughout the following 4.5 s. The theophylline- and caffeine-induced effect was rapid, t ransient, concentration dependent and gustatory tissue-specific. The effect could be partially suppressed in the presence of the soluble guanylyl cycl ase (GC) inhibitor 10 mu M ODQ and 30 mu M methylene blue but not 50 mu M L Y 83583 and boosted by nitric oxide donors 25 mu M NOR-3 or 100 mu M sodium nitroprusside. The proposed mechanism for this novel cGMP-mediated bitter taste signal transduction is cGMP production partially by the soluble GC an d caffeine-induced inhibition of one or several phosphodiesterases.